Li Shize, Wang Nini, Lou Jiyu, Zhang Xiaoman
Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
Department of Neurology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhenzhou, Henan 450007, P.R. China.
Exp Ther Med. 2015 Jun;9(6):2389-2393. doi: 10.3892/etm.2015.2391. Epub 2015 Mar 27.
The aim of this study was to investigate the expression of β-site APP-cleaving enzyme 1 (BACE1) in the hippocampal tissue of an insulin-resistant rat model, and thereby explore the roles of BACE1 and insulin resistance (IR) in the pathogenesis of Alzheimer's disease (AD). A total of 36 male Sprague-Dawley rats, aged 2 months, were randomly divided into three groups. These were an insulin-resistant (experimental) group, a high fat control group and a blank control group. The cognitive function and behavioral changes of the rats were tested by a Morris water maze experiment. Amyloid β (Aβ) deposition was detected by an immunohistochemical method. The expression levels of BACE1 in the rat hippocampal tissues were detected by enzyme-linked immunosorbent assay, western blotting and reverse transcription-quantitative polymerase chain reaction technology. The rats in the experimental group had evident learning and memory impairment, with significantly decreased learning memory. The modeling was successful; in the experimental group, the rats exhibited IR and their glucose metabolism was significantly abnormal. However, there was no characteristic pathology of AD. The expression of BACE1 in the brain tissue of rats in the experimental group was significantly higher than that in high fat control and blank control groups (P<0.01). In conclusion, the expression of BACE1 in the brain tissue of insulin-resistant rats increased, and IR was indicated to participate in the pathogenesis of AD.
本研究旨在探讨β-淀粉样前体蛋白裂解酶1（BACE1）在胰岛素抵抗大鼠模型海马组织中的表达，从而探究BACE1和胰岛素抵抗（IR）在阿尔茨海默病（AD）发病机制中的作用。选取36只2月龄雄性Sprague-Dawley大鼠，随机分为三组，即胰岛素抵抗（实验）组、高脂对照组和空白对照组。采用Morris水迷宫实验检测大鼠的认知功能和行为变化。采用免疫组化方法检测淀粉样β蛋白（Aβ）沉积。采用酶联免疫吸附测定、蛋白质印迹法和逆转录-定量聚合酶链反应技术检测大鼠海马组织中BACE1的表达水平。实验组大鼠出现明显的学习记忆障碍，学习记忆能力显著下降，造模成功；实验组大鼠表现出IR，其糖代谢明显异常，但无AD的特征性病理改变。实验组大鼠脑组织中BACE1的表达明显高于高脂对照组和空白对照组（P<0.01）。综上所述，胰岛素抵抗大鼠脑组织中BACE1的表达增加，提示IR参与AD的发病机制。
